Integration of metabolomics and gut microbiome to analyse the protective effect of Boletus aereus polysaccharide against LPS-induced colitis

Boletus aereus have biological effects such as anti-inflammatory, antioxidant and immunomodulatory effects. As medicines and functional foods, Boletus aereus has a long history of application. In order to explore the immunomodulatory mechanism of Boletus aereus polysaccharide (BAP) in the intestinal tract, the present study was conducted to construct a mouse model of colitis induced by LPS, and the preventive mechanism of Boletus aereus extract on LPS-induced intestinal inflammation in rats was analyzed by histopathological examination and biochemical analysis. Meanwhile, the immunomodulatory mechanisms were analyzed in combination with metabolomics and gut microbiomics. We found that BAP effectively reduced the levels of pro-inflammatory factors IL-6 and TNF-α and increased the levels of anti-inflammatory factor IL-10 in the serum of mice, and BAP suppressed the expression of TLR4/NF-ĸB/MAPK inflammatory signaling pathway in the colonic tissues, inhibited the expression of inflammatory vesicle NRLP3, and promoted the expression of NRF2/HO-1 signaling pathway, and elevated the SOD, T- AOC, and T-AOC levels. BAP decreased the expression of the TGF/Smad signaling pathway and decreased the expression of the fibrosis factors Collagen I Collagen III, α-SMA. The results indicated that Boletus edulis extract may exert immunomodulatory function by inhibiting TLR4/NF-ĸB/MAPK signaling pathway,and enhance the anti-oxidative stress ability by promoting the expression of NRF2/HO-1 signaling pathway. BAP altered the composition of gut microbiota in LPS-induced mice. In addition, Spearman's correlation coefficient showed a significant correlation between serum tyrosine metabolic pathway and gut microbiota species. The changes in gut microbiota and serum metabolites may partially explain the protective effect of BAP against colitis. In conclusion, these results suggest that BAP may be involved in the prevention of colitis disease at multiple levels, and also provide a theoretical basis for the development of Boletus aereus as an adjunctive functional edible for enteropathy.